This project is a series of basic and translational studies evaluating the mechanisms of traumatic peripheral neuropathic pain in animal models and patients with spontaneous pain and pain evoked by light touch (mechanical allodynia). Sensory testing with thermal, mechanical, and electrical stimuli and differential nerve blocks are used to differentiate peripheral from central mechanisms of neuropathic pain in symptomatic patients. Parallel studies are conducted in a human model of this condition in which the irritant capsaicin is injected intradermally to produce mechanical allodynia and spontaneous pain. An animal model previously developed in the Branch, the chronic constriction injury model, is used to better characterize sensory changes detected in humans and to further evaulate possible mechanisms of neuropathic pain. Observations from animal and clinical studies form the basis for a model of neuropathic pain that persistent nociceptive input can initiate and maintain altered central processing. The dramatic altered processing of input from A beta touch fibers in conditions of frank nerve injury likely forms a continuum of the severity of injury and the magnitude of neuropathic symptoms. Animal studies have evaluated the contribution of inflammation of the nerve following peripheral nerve injury to the development of neuropathic pain. Experimentally produced nerve inflammation in rats produced the same symptoms (mechanical allodynia, hyperalgesia, cold allodynia, and heat hyperalgesia) as observed with frank tissue damage in other animal models, suggesting that neuronal inflammation may play a significant role in clinical neuropathic pain syndromes. Continuing studies are evaluating mechanisms of neuropathic pain in different clinical conditions and related animal models to better understand the etiology and management of chronic, debilitating pain caused by nerve injury.